The Simpsons: Hit & Run is a video game released on September 16, 2003 for the PlayStation 2, GameCube and Xbox in North America, with the Windows port released on November 13, in the region. October 31 in PAL regions, with the Windows port released on November 21, in the region and December 25, in Japan. It was made by Vivendi Universal and was created by Radical Entertainment. All of the series's cast had auditioned in the game.

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Following the release of a new Buzz Cola, strange events are happening all around Springfield. Homer notices a surveillance van spying on him and Bart disappears into a bright light. When Bart is found he is in a stupor but returns to normal when shown Buzz Cola. He reveals that he saw it on an alien spaceship and that it is used to control minds. Kang and Kodos are found to be responsible as they plan to make people go insane by infusing the cola into Springfield's water supply which will also have the ability to raise the dead. Playing as the Simpson family (sans Maggie) and Apu, they go around Springfield investigating the areas of such events to find out what is happening and the secret behind it.

On October 25, wasp-like cameras and black vans are suddenly appearing in Springfield. One enters the Simpsons' residence at Evergreen Terrace. It disturbs Homer's nap, and he crushes it. When he wakes up, he finds levitating coins and sees a commercial for the "New and Improved" Buzz Cola, and decides to go to the Kwik-E-Mart.

Homer goes to the convenience store to get a bucket of ice cream with mini-pies and a can of Buzz Cola. He then does a favor for Lisa by giving her the science project before Skinner reaches the school. Afterwards, Homer gives back Flanders' stuff that he "borrowed" from before. Marge later reminds Homer that this day was the examination by Smithers. Lenny tells him that Smithers is down at the Kwik-E-Mart, and he decides to destroy his car. To do so, he buys the Plow King snowplow from Barney. When the convertible is destroyed, Homer goes to work. However, he can't take a nap because of the camera in his office, and he destroys all of the power couplings, but that ends up sending the workers home. Back home, Homer sits down and watches TV, but he notices a black van outside of his house, and decides to follow it. It stops at Burns' mansion, and Homer thinks it belongs to Mr. Burns. He then attempts to warn Marge, but she is busy trying to destroy a new game, the sequel to Bonestorm. After Homer helps her, he attempts to warn Carl, but he's drunk. Realizing that Smithers would warn Burns of his attempts to accuse him, Homer races Smithers to the mansion and confronts Mr. Burns, who tells him that the vans are part of a pizza delivery service. Homer is promptly fired by Burns, who releases the hounds on him.

The next day, Bart attempts to get a copy of the Bonestorm 2 game, but he has to avoid Principal Skinner to get to the Try-N-Save. When he gets there, Jimbo reveals that he "bought" the last one in stock with four-finger discount, and unbeknownst to Bart, the rest were destroyed by Marge.
Bart mopes to Kearney, but he tells Bart that fireworks are the new trend. With Kearny's advice, he collects fireworks from Otto, Moe, Snake and Ralph. Bart is nearly caught by Chief Wiggum, so he goes on his quest for Bonestorm 2 again. Bart then helps Comic Book Guy to get to the Java Server before a nerd to report about a new movie on his web page, and when they arrive, Comic Book Guy tells Bart Professor Frink could have a copy of the game. Frink tells Bart he could make a Truckasaurus by collecting a WWII radio and a satellite dish. Bart goes to Herman's Military Antiques, but the store was robbed by Snake. He then races Snake for the radio. Bart then helps Cletus deliver flatmeat to the Krusty Burger to get a satellite dish. When Bart returns, Professor Frink tells him that he forgot the blender. He goes to Dr. Nick to get a blender, but first, he has to do him a favor; his monkeys escaped and wants them back. Bart buys the Mr Plow snowplow from Homer, collects the monkeys and he gets the blender. When Bart collects all of the items however, Professor Frink complains that there are too many cell phone users, and the interference would cause it go on a rampage and kill people in the ensuing destruction, and he claims that his insurance is too high to pay for all of that. Bart then destroys the cars with cell phones and gets to see the Trucksaurus. After nearly getting crushed by it, he gets kidnapped by aliens.

The disappearance of Bart puzzled everyone, and on the 27th, Lisa decides to look for her brother. First, she goes to Comic Book Guy for answers, but he wants to retrieve a controversial issue of the Itchy and Scratchy where they kiss. she helps him out. Next, Lisa goes to Milhouse but he keeps on taking her to random places to ask her to the dance and Lisa gets annoyed and tells him its not a good time and milhouse whines .Lisa then goes to Apu, but he needs help destroying flatmeat that Cletus was delivering to the Krusty Burgers. Lisa is then told by Grampa at the observatory that he saw Bart's lucky red hat fall out of a sedan, and with Otto's school Bus, she wrecks it. She then goes down to Monty Burns Casino and assists Chief Wiggum in taking down Snake with "three strikes", in exchange for information about Bart. He reports that he saw a lot of strange stuff around the docks. Lisa then asks Captain McCallister about these suspicious appearances, but to jog his memory, she has to deliver fish to restaurants. Instead of delivering them, she sets them free. The Captain then tells Lisa that Bart was in a limo, but when she destroys it, he told her that he was actually aboard the C-Spanker. Lisa then boards the ship, and finds Bart with soiled pants and muttering unintelligible gibberish.

On the 28th, Marge decides to investigate the cause of Bart's insanity. A clue could be a suspicious crop circle. She questions Chief Wiggum, but he needs some donuts even though Lard Lad is closed. Marge then collects donuts from a donut truck. After that, Chief Wiggum tells Marge the crop circle is near Cletus's shake but when she gets there, Cletus mistakes her for a reporter, so Marge must follow him and collect his items. Afterwards, Cletus agrees to help Marge if she helps him with collecting ketchup packets. Marge agrees but changes into a prison uniform to avoid getting her clothes dirty. After she has helped Cletus, he tells her to try talking to an old person. Marge arrives at the cementery to talk to Hans Moleman, who says she should talk to Grampa, but must be quick because the Springfield Retirement Castle shuts in a few minutes. Marge gets to Grampa but he needs his medication, which some bullies stole and gave to a man in a black car which is the alien's car. Marge returns and Abe has fallen asleep. After he wakes up, grandpa says that the crop circles are shaped like the image of the Buzz Cola logo. She returns to Bart, who tells her the aliens used it as mind control, so Marge goes and investigates as officer Marge. She then tells Apu about the cola and she destroys three cola trucks. She returns home, where Chief Wiggum is wating. After avoiding him, Marge goes home to her family.

Apu now decides to investigate. He follows a Buzz Cola truck, which takes him to the Legitimate Businessman's Social Club, where Louie tells him the cola is related to the museum, but if he tells this to someone, they will go for his family. Apu then prevents the mafia to reach the hospital, where Doctor Hibbert tells him his babies need diapers, so he gets them from the Shelbyville family. Krusty tells Apu to dress himself as an American to follow the police track to get to a criminal that would help him know more about the cola. He gets to Snake, who wants Apu to collect trash bins and destroy an armored truck for "community service". This was actually to get money. Apu then goes for Bart, who helps him get to the museum before it closes. There, they discover this is a plan from Kang and Kodos, who gave Buzz Cola to Earthicans to make them crazy and the audience for their TV show raises. They comment each other they will give laser guns to people at the Springfield Squidport so they shoot each other and make their TV show the most popular one in the galaxy.

Bart wants Apu to help him, but he rejects, so he asks Otto, who is going to Krustylu Studios taking kids along the way. Bart then asks Barney (as the security guard) where is Krusty. He suggests following a Itchy and Scratchy Movie Lorry that goes to the Springfield Squidport. Eventually, it takes Bart to Krusty, who doesn't believe Bart's story about aliens. He decides to find someone who does believe him, like from Professor Frink. After following him to the observatory, he tells Bart to find a laser as proof. He knocks one of the Duff Lorries full of boxes with lasers and destroys them. He picks up one of the lasers as proof, but Skinner takes it. After Bart destroys his car and takes the laser back, he goes for Krusty. Now he believes him and tells him to destroy the laser stands. Bart buys the Globex Super Villain Car from Kearney and runs over all of the stands. Now, Bart goes for Homer and asks him for help to get rid of the lasers. They have to arrive to the Duff Brewery before one of the black saloon from before reaches it first. When they get to there, they see a spaceship come from inside the factory. Kang and Kodos tell Homer and Bart that their TV show will raise its ratings because they have dropped Buzz Cola in the cemetery and the dead people will raise from the ground.

Springfield has transformed into a creepy city full of witches, ghosts and zombies everywhere. All of the buildings and houses have been transformed into Halloween places, with pumpkins at the entrances and on the streets. Lisa wants Homer to get rid of the zombies, so he goes and gets things to fight them. Comic Book Guy then suggests Homer to look for the aliens hideout, which is the Springfield Nuclear Power Plant. There, Homer finds Professor Frink, who tells him the Rigellians weakness is nuclear waste, so they both deliver nuclear waste to the spaceship at the school. Later, Lisa tells Homer Mr. Burns must have some nuclear waste. He gives Homer a map to all of the nuclear waste he has hidden in the city. Homer uses his car, Frink's Hover Car, Snake's Bandit and Grampa's World War II (With Rocket) car to deliver nuclear waste to the spaceship and destroy it. The day after, everything is back to normal. Homer thinks all was just a hotdog dream. Bart informs him about some men in the door. Those men are Rigelians, who congratulate Homer for Kang and Kodos' TV show. In the Heaven, Kang and Kodos watch everything. The game ends with Kang screaming because of the Hit & Run logo appearing, signifying the credits.

After the dialogue between the playable character and the mission character ends, this screen appears

The main menu, with Homer sleeping and the wasp camera he destroyed. When some time has passed, a random character appears outside the window and says something

Hit & Run focuses primarily on driving missions. It employs the "sandbox" format, featuring a third-person view, an explorable environment, and drivable vehicles similar to the Grand Theft Auto series. Unlike Grand Theft Auto where most cars can be hijacked or stolen, instead, the player's character rides in the passenger's seat of another vehicle while the owner drives. The game features a "Hit & Run meter" that brings the police after the player if it gets too high; if the player is captured by the police, (s)he is fined 50 coins. In the first 3 levels, only one police car is deployed to chase the player, but starting from level 4, two police cars are dispatched in pursuit.

Progressing though the various story levels allows the player to control Homer, Lisa, Marge, Bart, and Apu; many other Simpsons characters such as Chief Wiggum and Professor Frink appear in non-playable roles, but will also drive you in some missions.

In addition to the story missions, players can optionally participate in "bonus" missions or races which typically award unlockable cars for successful completion. Coins, the currency in the game, are acquired by hitting objects such as trees or mailboxes, destroying wasp cameras or Buzz Cola machines, or simple collection (many coins are simply scattered throughout each level). Players can use coins to purchase new vehicles or outfits for the current character; many of these can be traced directly to specific episodes of The Simpsons (e.g. Bart's Space Shuttle-shaped Honor Roller soapbox racer or Marge's police uniform). Many of the cars come from The Simpsons Road Rage.

To complete the game 100%, the player must complete all missions including the bonus missions and perform another series of tasks:

A number of "collector cards" depicting objects, characters, or scenes from the series are placed in each level, usually in hard-to-access areas. Collecting all of these cards in a level unlocks a track that can be played in a slot car-like racing game, and collecting all of the cards in the game unlocks an original Itchy & Scratchy short, "500-Yard Gash".

Three street race missions are assigned each level by Milhouse, Nelson and Ralph (with the exception of Level 7 where they are assigned by zombies). If the player wins all of them in a level, they unlock a car. In addition, two cars are sold per level by Gil and a secondary character such as Otto sells another car which can sometimes be compulsory for certain missions.

There are three alternate outfits for the player character to buy in each level.

There are a certain number of wasp cameras in every level to be destroyed which become increasingly difficult to beat as the game progresses.

There are a number of small interactable "gags" in every level where a short animation occurs. An example of this is when the player causes an explosion in Homer's office.

The game received generally favorable reviews, an average of 81/100 score from critics. The game did well in sales as well, selling over 5.5 million copies worldwide as of June 2009. The game received an editor's choice award from GameSpy and it won the award for Fave Video Game at the 2004 Nickelodeon Australian Kids' Choice Awards.